Retinoic Acid May Enhance Chemo In Ovarian Ca Cells

Retinoic Acid May Enhance Chemo In Ovarian Ca Cells

SAN FRANCISCO--Retinoic acid appeared to enhance the efficacy
of cisplatin (Platinol) and paclitaxel (Taxol) in two of three
ovarian cancer cell lines tested, James R. Bosscher, MD, said
in his poster presentation at the Society of Gynecologic Oncologists
meeting.

Because cisplatin and paclitaxel are the most effective agents
against epithelial ovarian cancer, any agent that improves their
efficacy deserves further investigation, Dr. Bosscher told Oncology
News International. He pointed out that retinoic acid, a derivative
of vitamin A, has been shown to be an important influence in cell
differentiation, as well as an effective treatment for other types
of early cancers.

Dr. Bosscher and his colleagues at the University of Louisville
School of Medicine looked at the effects of retinoic acid on three
cell lines, two standard epithelial ovarian cancer cell lines
(SKOV-3 and OVCAR-3) and UL-1, which was developed at Louisville
from the ascites of an ovarian cancer patient.

When the cancer cell lines were exposed to retinoic acid alone,
the compound interfered with the doubling rate of the OVCAR-3
cell line. Retinoic acid by itself produced no significant effects
on the other two cell lines, Dr. Bosscher reported.

When paclitaxel and cisplatin were added to OVCAR-3 and UL-1 cell
lines that had previously been treated with retinoic acid, the
cell kill rate of the two chemotherapies improved. The amount
of either cisplatin or paclitaxel required to kill 50% of the
cancerous cells was significantly reduced.

Dr. Bosscher noted that the effect of retinoic acid seems to be
related to the presence or absence of cell membrane receptors
for the compound. In the SKOV-3 ovarian cancer cell line, which
has fewer retinoic acid receptors, retinoic acid appeared to protect
cancer cells from the effects of chemotherapy. The amount of drug
required to kill 50% of the cancer cells increased when retinoic
acid was added--significantly in the case of cisplatin and slightly
for paclitaxel.

"The next step is to move beyond in vitro cell culture studies
to determine the effect of this treatment in mice, with an eye
toward taking the trials to phase I studies a few years down the
road," Dr. Bosscher said.

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